Therapeutic trials of L-5-hydroxytryptophan (L-5HTP), the precursor of serotonin, in combination with the peripheral decarboxylase inhibitors, carbidopa and benserazide, will be evaluated in patients with diseases associated with myoclonic muscle movements (eg. intention myoclonus, progressive myoclonus epilepsy, essential myoclonus etc.). The metabolism of L-5HTP in these patients will be evaluated by measurement of cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5HIAA) and blood serotonin, 5HIAA and 5HTP. The dosage schedule, safety and clinical and biochemical side effects of these drugs will be established. Therapeutic trials of fluoxetine, a serotonin uptake inhibitor, phenoxybenzamine, an alpha receptor blocker and the anticonvulsant clonazepam in patients with myoclonus are proposed. We have found that oral administration of p,p'-DDT produces stimulus sensitive myoclonus in mice and rats which has many similarities to the human disorder. L-5HTP and other serotonin agonists reduce the intensity of p,p'-DDT induced myoclonus. The biochemical changes inducing myoclonus and the localization of the neuronal pathways involved will be investigated in this animal model. We discovered that another compound p-chlorophenylethylamine (p-CPEA) decreases p,p'-DDT-induced myoclonus and increases the concentration of brain 5-hydroxy-indoleacetic acid (5HIAA). Further biochemical studies of the mechanism(s) of action of p-CPEA are proposed in this grant.